Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: PegIFN/RBV; Drug: BI 201335 NA 120mg QD / LI; Drug: BI 201335 NA 240 mg QD; Drug: BI 201335 NA 240 mg BID; Drug: BI 201335 NA 240 mg QD / LI; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00774397

2008-003538-11 (EudraCT Number)

1220.5

Details and patient eligibility

About

The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.

Enrollment: 719 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL >=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception

Exclusion criteria

Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value > 100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin > 1.5x ULN wiht ratio of direct/indirect >1. ALT or AST levels > 5x ULN INR prolonged to >1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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719 participants in 7 patient groups, including a placebo group

240 mg QD TN

Experimental group

Description:

240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

240 mg QD / LI-TN

Experimental group

Description:

240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients

Treatment:

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD / LI

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Placebo

Placebo Comparator group

Description:

Placebo once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment-naive (TN) patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: Placebo

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

120 mg QD / LI-TN

Experimental group

Description:

120 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in (LI) phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), followed by an additional 24 weeks of PegIFN/RBV in treatment naive (TN) patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 120mg QD / LI

Drug: PegIFN/RBV

240 mg QD TE

Experimental group

Description:

240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV in treatment experienced (TE) patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

240 mg QD / LI-TE

Experimental group

Description:

240 mg BI 201335 NA (Faldaprevir) once daily (QD) combined with PegIFN/RBV for 24 weeks, with a 3-day lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 (Faldaprevir) three days after first administration of PegIFN/RBV), success-dependently followed by re-randomisation to stop or to an additional 24 weeks of PegIFN/RBV in treatment-experienced (TE) patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg QD

Drug: BI 201335 NA 240 mg QD

Drug: PegIFN/RBV

240 mg BID / LI-TE

Experimental group

Description:

240mg BI 201335 NA (Faldaprevir) twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients

Treatment:

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: BI 201335 NA 240 mg BID

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV

Drug: PegIFN/RBV